Tailored Therapy After Kasai Procedure Improves Bile Drainage

Improving Bile Drainage in Biliary Atresia with Customized Postoperative Therapy

The use of a customized protocol for biliary atresia patients after receiving the Kasai procedure greatly improves bile drainage in these patients and avoids the need for a liver transplant.

Physicians at the Pediatric Liver Care Center at Cincinnati Children’s found potential benefits from administering postoperative antibiotics and corticosteroids, says Anna Peters, MD, Ph.D.

The team published their findings in “Customized postoperative therapy improves bile drainage in biliary atresia: A single center preliminary report” in the Journal of Pediatric Surgery, in November 2022.

Combining Antibiotics and Corticosteroids After Kasai Procedure

Biliary atresia is the most common cause of end-stage liver disease in children. When the bile ducts are blocked, bile does not travel from the liver to the small intestine. Biliary atresia causes jaundice and pale stools. If left untreated, the blockage can cause cirrhosis of the liver and requires a liver transplant.

The Kasai procedure is a surgical technique that removes the diseased bile ducts and connects the small intestine directly to the liver to restore bile drainage. It is the standard of care for biliary atresia and produces the best outcome when performed as soon as possible after the diagnosis, ideally within 45 days after birth.

Historically, 50 percent of patients treated at Cincinnati Children’s achieved successful bile drainage immediately after Kasai or within three months.

“We wanted to improve those outcomes,” Peters says because half of the patients did not establish bile flow or see a reduction in jaundice. 

The antibiotic plus corticosteroid treatment improved post-Kasai drainage rates to 80 percent.

All babies who received the Kasai procedure and this new protocol at Cincinnati Children’s in the last calendar year showed positive bile drainage, and none were listed for a liver transplant, Peters says.

“Our success rates are 100 percent,” she says.

New Protocol Stems from Findings in Earlier Studies

Physicians are not completely sure why the antibiotic plus corticosteroid protocol works on a biological level.

They knew that using corticosteroids after the Kasai procedure might provide a small clinical benefit in children younger than 45 days old, Peters says.

But in general, steroid use does not show statistically significant treatment differences in bile drainage at 6 months. This is evidenced in the START (Steroids in Biliary Atresia Randomized Trial) trial, a multicenter, double-blind study that ended in 2013.

The new protocol is based on several studies in mice and humans, Peters says. The work suggests that:

• Biliary atresia is an inflammatory condition.
• Some bacteria are present and activate the immune system.
• These bacteria may cause continued damage to the bile ducts after surgery.

The protocol uses steroids to decrease inflammation and swelling combined with antibiotics to help reset the bacterial composition and prevent infection.

More Research, Collaboration Ahead

Cincinnati Children’s now administers the new protocol for all patients who receive the Kasai procedure. 

Further research plans include more biological studies to fully understand how corticosteroids and antibiotics affect the babies’ immune systems.

The Liver Center team plans to continue sharing information about the postoperative Kasai therapy with colleagues at other pediatric medical centers, Peters says.

“In theory, these are tools that are available everywhere, and we would hope to improve Kasai outcomes for babies everywhere,” she says.

Sindhu Pandurangi, MD, chief fellow for the Division of Gastroenterology, Hepatology, and Nutrition, presented information about the customized postoperative therapy protocol at the 2022 North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition conference. Pandurangi is the first author of the published study.

But it’s not just about the medicines. One thing that makes the protocol work is making the correct diagnosis as early as possible after referral, says Alexander Miethke, MD, Liver Transplant Program director.

“The team has put in place several measures,” Miethke says. “Those steps include a fast track for visit with a liver doctor, use of novel serum MMP7 testing, and scheduling surgery within days after establishing the diagnosis.”

Another reason the protocol is successful is the multidisciplinary collaboration and care from medical and surgical specialists that patients receive.

“At some centers, only surgeons manage babies with biliary atresia,” Peters says. “Working together and making joint decisions about implementing this protocol makes the difference.”